Project Summary/Abstract Aging is often associated with learning and memory impairments. Yet, some aged individuals remain free of any impairment. The current project seeks to investigate the neurobiological mechanisms that underlie the aging-related impairments and what separates those with impairments (aged impaired--AI) from those without (aged unimpaired--AU). Previous research has focused on the hippocampus, a major region necessary for memory formation. The current project will focus on the entorhinal cortex (EC), another important region for memory, as it serves as the relay station between cortical regions and the hippocampus. The EC is not only important for supporting memory, but is also a site for major aging-related changes. For example, within normal aging, EC volume is directly inversely correlated with poorer memory performance. Alzheimer?s disease, a neurodegenerative disorder whose major risk factor is increasing age, initially manifests itself within the EC. The current project will focus on the lateral division of the EC. The lateral EC is suggested to support the formation of temporal associative memory, a task on which many aged individuals are impaired. These converging pieces of evidence suggest the presence of neurobiological changes within the LEC that support learning and that altered neuronal physiology with aging may underlie the inability to undergo those changes, thus resulting in learning deficits. The current project, therefore, seeks to identify the biophysical alterations that occur in LEC neurons from young and aged animals that successfully learn (Y and AU) and from those that cannot (AI). The project will focus on changes within the neurons that project via the perforant path to the dentate gyrus, as the perforant path makes up the first step of the trisynaptic loop, the classic circuit for memory formation in the hippocampus. While previous studies have electrophysiologically characterized the neurons of the LEC, the identity of the perforant path neuron has not yet been definitively identified. I will, therefore, first establish the identity of the perforant path neuron by injecting a retrograde fluorescent tracer into the dentate gyrus of young and aged animals (Aim 1). The fluorescent tracer will confirm the morphology of the neuron and also allow for targeting during whole-cell current clamp recordings, allowing for confirmation of the electrophysiological profile. During whole cell recordings, I will also measure neuronal excitability, as previous research has determined that aging-related changes in neuronal excitability within the hippocampus have prevented successful learning in aged animals. I will then train young adult and aged animals on a temporal associative learning task in order to measure learning-related changes in excitability in the perforant path neuron (Aim 2). Recordings will reveal how learning is supported in the LEC of Y and AU animals and also identify mechanisms that prevent successful learning in AI animals. The results of this study will provide a target for potential therapeutics in alleviating aging-related learning deficits and dementia.